title: Blood pressure and not uraemia is the major determinant of arterial stiffness and endothelial dysfunction in patients with chronic kidney disease and minimal co-morbidity.
abstract: BACKGROUND
  Patients with chronic kidney disease (CKD) have increased risk of cardiovascular disease to which co-morbidity and associated conventional risk factors contribute. We hypothesised that arterial stiffness (AS) and endothelial dysfunction (ED), as surrogates of cardiovascular risk, would worsen as renal function declined even in patients without co-morbidity and that this would relate to emerging cardiovascular risk factors.
  
  
  METHODS
  Carotid-femoral pulse wave velocity (PWV), as a measure of AS, and flow-mediated dilatation (FMD) of the brachial artery, as a measure of ED, were assessed in CKD patients without established cardiovascular disease or diabetes mellitus.
  
  
  RESULTS
  PWV increased linearly as renal function declined (r(2) = 0.08, p < 0.01) whereas FMD was reduced only in patients with advanced kidney disease. In multivariable analysis, blood pressure was the major determinant of PWV and FMD. High-sensitivity C-reactive protein and asymmetric dimethylarginine, and isoprostanes and endothelin-1, were independent predictors of PWV and FMD, respectively. However, renal function did not independently predict either AS or ED.
  
  
  CONCLUSIONS
  These findings suggest that declining renal function, in the absence of significant co-morbidity, is associated with progressive arterial stiffness, but only patients close to dialysis exhibit endothelial dysfunction. Whilst blood pressure remains the major determinant of PWV and FMD, inflammation, oxidative stress and endothelin-nitric oxide balance contribute to cardiovascular risk, in this non-comorbid cohort.
authors.affiliation: Clinical Pharmacology Unit, British Heart Foundation, Centre of Research Excellence, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Pajaree
authors.initials: P
authors.lastname: Lilitkarntakul
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhaun
authors.forename: Vanessa
authors.initials: V
authors.lastname: Melville
authors.forename: Scott
authors.initials: S
authors.lastname: Blackwell
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Talwar
authors.forename: Barbara
authors.initials: B
authors.lastname: Liebman
authors.forename: Takae
authors.initials: T
authors.lastname: Asai
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pollock
authors.forename: Jane
authors.initials: J
authors.lastname: Goddard
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001916:Brachial Artery / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000032:analysis; D002339:Carotid Arteries / Q000503:physiopathology*; D016022:Case-Control Studies; D002908:Chronic Disease; D015897:Comorbidity; D003187:Compliance; D003430:Cross-Sectional Studies; D018450:Disease Progression; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D006801:Humans; D028421:Isoprostanes / Q000097:blood; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D011446:Prospective Studies; D011673:Pulsatile Flow; D018570:Risk Assessment; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D014511:Uremia / Q000453:epidemiology / Q000503:physiopathology*; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D028421:Isoprostanes; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine